Systemic impact on secondary brain aggravation due to ischemia/reperfusion injury in post-cardiac arrest syndrome: a prospective observational study using high-mobility group box 1 protein

Atsunori Sugita, Kosaku Kinoshita, Atsushi Sakurai, Nobutaka Chiba, Junko Yamaguchi, Tsukasa Kuwana, Nami Sawada, Satoshi Hori

Ischemia/reperfusion injury (I/R) is an important pathophysiology of post-cardiac arrest syndrome (PCAS) against multiple organ dysfunction and mortality. The inflammatory response in PCAS causes systemic I/R. The purpose of this study was to demonstrate the pathophysiology of systemic I/R for secondary brain damage using the biomarkers high-mobility group box 1 (HMGB1), neuron-specific enolase (NSE), and interleukin-6 (IL-6). This study was designed as a single-institution prospective observational study. Subjects were observed for 90 days, and neurological outcome was classified according to the Glasgow-Pittsburgh Cerebral Performance Categories Scale (CPC). Serum HMGB1, NSE, and IL-6 were evaluated for variability, correlation with each biomarker, or the Sequential Organ Function Assessment (SOFA) score and CPC at return of spontaneous circulation at 0, 24, 48, and 168 h. A total of 128 patients were enrolled in this study. Initial HMGB1 correlated with CPC (ρ = 0.27, p = 0.036) and SOFA score (ρ = 0.33, p < 0.001). The early phase of HMGB1 (0-24 h), all phases of IL-6, and the delayed phase of NSE (24-168 h) manifested poor neurological outcome. HMGB1 showed a significant correlation with NSE (ρ = 0.29, p = 0.002 at 0 h; ρ = 0.42, p < 0.001 at 24 h) and IL-6 (ρ = 0.36, p < 0.001 at 24 h). Serum HMGB1 for first 24 h after cardiac arrest was significantly correlated with SOFA score, NSE, and IL-6. This result suggests that systemic I/R may contribute to secondary brain aggravation. It is expected that research on HMGB1 focused on systemic I/R will help prevent aggravating neurological outcomes.